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2014 Grants - Arkin
Inhibitors of Caspase-6 as Potential Alzheimer’s Therapeutics
Michelle Arkin, Ph.D.
University of California at San Francisco
San Francisco, California
2014 Investigator-Initiated Research Grant: Discovery-Validation of Therapeutic Targets for Developing Novel Interventions for Alzheimer’s Disease
A characteristic feature of Alzheimer’s disease is neurofibrillary tangles in the brain. One of the main components of tangles is the protein tau, which normally functions to help maintain cell structure but becomes abnormally altered during Alzheimer’s disease. One step in the alteration of tau is the cutting of tau by another protein known as caspase-6. There is evidence that preventing caspase-6 from cutting tau can reduce the formation of neurofibrillary tangles and subsequent nerve cell damage associated with disease progression.
Michelle Arkin, Ph.D., and colleagues have developed several drug candidates that reduce the activity of caspase-6. They propose a series of experiments to test each compound for its ability to inhibit caspase-6 activity, preventing the cutting of tau and potentially reducing the formation of neurofibrillary tangles in nerve cells. For these studies, the researchers will use nerve cells from mice that have been genetically altered to have Alzheimer’s-like brain changes. These studies may lead to the development of new drug candidates for testing in humans for their ability to prevent or slow the progression of Alzheimer’s disease.